Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study

Non-Invasive Characterization of Atrio-Ventricular Properties during Atrial Fibrillation

The atrio-ventricular (AV) node is the primary regulator of ventricular rhythm during atrial fibrillation (AF). Hence, ECG based characterization of AV node properties can be an important tool for monitoring and predicting the effect of rate control drugs. In this work we present a network model of the AV node, and an associated workflow for robust estimation of the model parameters from ECG. The model consists of interacting nodes with refractory periods and conduction delays determined by the stimulation history of each node. The nodes are organized in one fast pathway (FP) and one slow pathway (SP), interconnected at their last nodes. Model parameters are estimated using a genetic algorithm with a fitness function based on the Poincare plot of the RR interval series. The robustness of the parameter estimates was evaluated using simulated data based on ECG measurements. Results from this show that refractory period parameters R{min}{SP} and Delta R{SP} can be estimated with an error (meanpm std) of 10pm 22 ms and-12.6pm 26 ms respectively, and conduction delay parameters D{min,tot}{SP} and Delta D{tot}{SP} with an error of 7pm 35 ms and 4pm 36 ms. Corresponding results for the fast pathway are 31.7pm 65 ms, -0.3pm 77 ms, and 1 7pm 29 ms,43pm 109 ms. This suggest that AV node properties can be assessed from ECG during AF with enough precision and robustness for monitoring the effect of rate control drugs

Non-invasive Characterization of Human AV-Nodal Conduction Delay and Refractory Period During Atrial Fibrillation

During atrial fibrillation (AF), the heart relies heavily on the atrio-ventricular (AV) node to regulate the heart rate. Thus, characterization of AV-nodal properties may provide valuable information for patient monitoring and prediction of rate control drug effects. In this work we present a network model consisting of the AV node, the bundle of His, and the Purkinje fibers, together with an associated workflow, for robust estimation of the model parameters from ECG. The model consists of two pathways, referred to as the slow and the fast pathway, interconnected at one end. Both pathways are composed of interacting nodes, with separate refractory periods and conduction delays determined by the stimulation history of each node. Together with this model, a fitness function based on the Poincaré plot accounting for dynamics in RR interval series and a problem specific genetic algorithm, are also presented. The robustness of the parameter estimates is evaluated using simulated data, based on clinical measurements from five AF patients. Results show that the proposed model and workflow could estimate the slow pathway parameters for the refractory period, (Formula presented.) and ΔRSP, with an error (mean ± std) of 10.3 ± 22 and −12.6 ± 26 ms, respectively, and the parameters for the conduction delay, (Formula presented.) and (Formula presented.), with an error of 7 ± 35 and 4 ± 36 ms. Corresponding results for the fast pathway were 31.7 ± 65, −0.3 ± 77, 17 ± 29, and 43 ± 109 ms. These results suggest that both conduction delay and refractory period can be robustly estimated from non-invasive data with the proposed methodology. Furthermore, as an application example, the methodology was used to analyze ECG data from one patient at baseline and during treatment with Diltiazem, illustrating its potential to assess the effect of rate control drugs

Drug Dependent Circadian Variations in AV-nodal Properties During Atrial Fibrillation

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node, which can be affected using β-blockers or calcium channel blockers, often chosen empirically. Thus, characterization of the AV nodal conduction properties could contribute to personalized treatment of AF. We have created a mathematical network model of the AV node where continuous estimation of the refractory period and conduction delay from 24-hour ambulatory ECGs from patients with permanent AF (n=59) was achieved using a problem-specific genetic algorithm. Circadian variations in the resulting model parameter trends were quantified using cosinor analysis, and differences between treatment with β-blockers and calcium blockers were assessed using a linear-mixed effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. For the β-blockers, an additional decrease in circadian variation for parameters representing conduction delay was observed. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. The proposed method enables analysis of circadian variation in AV node conduction delay and refractoriness from 24h ambulatory ECG, which can be used to monitor and possibly predict the effect of rate control drugs

ECG based assessment of circadian variation in AV-nodal conduction during AF—Influence of rate control drugs

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node. These properties can be affected using β-blockers or calcium channel blockers, mainly chosen empirically. Characterization of individual AV-nodal conduction could assist in personalized treatment selection during AF. Individual AV nodal refractory periods and conduction delays were characterized based on 24-hour ambulatory ECGs from 60 patients with permanent AF. This was done by estimating model parameters from a previously created mathematical network model of the AV node using a problem-specific genetic algorithm. Based on the estimated model parameters, the circadian variation and its drug-dependent difference between treatment with two β-blockers and two calcium channel blockers were quantified on a population level by means of cosinor analysis using a linear mixed-effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. An additional decrease in circadian variation for parameters representing conduction delay was observed for the β-blockers. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. These differences could be important in treatment outcome, and thus quantifying them could assist in treatment selection

Circadian variation of variability and irregularity of heart rate in patients with permanent atrial fibrillation: Relation to symptoms and rate-control drugs.

The aim of this study is to evaluate the diurnal variation of the variability and irregularity of the heart rate (HR) in patients with permanent atrial fibrillation (AF), with and without rate-control drugs. Thirty-eight patients with permanent AF were part of an investigator-blind cross-over study, comparing diltiazem, verapamil, metoprolol, and carvedilol. We analyzed five Holter recordings per patient: at baseline (no rate-control drug) and with each of the four drug regimens. HR, variability (standard deviation, pNN20, pNN50, pNN80, and rMSSD) and irregularity (approximate (APEn) and sample entropy) parameters were computed in 20-minute long non-overlapping segments. Circadian rhythmicity was evaluated using the cosinor analysis to each parameter series, that is characterized by the 24-h mean (MESOR) and the excursion over the mean (the amplitude). Arrhythmia-related symptoms were assessed by a questionnaire measuring symptoms severity (SS) and frequency (SF). HR and variability parameters showed a significant circadian variation in most patients, whereas only a small minority of the patients had circadian variation of irregularity parameters. The patients with circadian ApEn at baseline had more severe symptoms (SS = 9±4 vs. 6±5, p<0.05; circadian vs. non-circadian variation). All drugs decreased the MESOR of HR and increased the MESOR of variability parameters. Only carvedilol and metoprolol decreased the normalized amplitude over the 24-h of all parameters and HR. In conclusion, HR and RR variability parameters present a circadian variation in patients with permanent AF, whereas few patients demonstrated circadian fluctuations in irregularity parameters, suggesting different physiological mechanisms

Rate-Control Drugs Affect Variability and Irregularity Measures of RR Intervals in Patients with Permanent Atrial Fibrillation

Heart Rate Variability and Irregularity During AF IntroductionIrregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate-control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF. Methods and ResultsSixty patients with permanent AF were part of an investigator-blind cross-over study, comparing 4 rate-control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20-minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 47 milliseconds, carvedilol 229 +/- 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 +/- 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 +/- 84; P < 0.05 vs. baseline, diltiazem 256 +/- 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only -blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 +/- 0.13, carvedilol 1.92 +/- 0.09; P < 0.05 vs. baseline, metoprolol 1.93 +/- 0.08; P < 0.05 vs. baseline, verapamil 1.86 +/- 0.22 ns, diltiazem 1.88 +/- 0.16 ns). ConclusionModification of AV node conduction by rate-control drugs increase RR variability, while only -blockers affect irregularity

DataSheet1_ECG based assessment of circadian variation in AV-nodal conduction during AF—Influence of rate control drugs.PDF

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node. These properties can be affected using β-blockers or calcium channel blockers, mainly chosen empirically. Characterization of individual AV-nodal conduction could assist in personalized treatment selection during AF. Individual AV nodal refractory periods and conduction delays were characterized based on 24-hour ambulatory ECGs from 60 patients with permanent AF. This was done by estimating model parameters from a previously created mathematical network model of the AV node using a problem-specific genetic algorithm. Based on the estimated model parameters, the circadian variation and its drug-dependent difference between treatment with two β-blockers and two calcium channel blockers were quantified on a population level by means of cosinor analysis using a linear mixed-effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. An additional decrease in circadian variation for parameters representing conduction delay was observed for the β-blockers. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. These differences could be important in treatment outcome, and thus quantifying them could assist in treatment selection.</p

Non-invasive assessment of the effect of beta blockers and calcium channel blockers on the AV node during permanent atrial fibrillation

We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data